Colorectal cancer is a serious complication in patients with ulcerative colitis or Crohn's disease. Early age at diagnosis, the extent and severity of colonic disease, the presence of primary sclerosing cholangitis, and/or a family history of cancer represent independent risk factors for the development of colorectal cancer. Aspirin has been found to exert chemopreventive effects in colon cancer, but the mechanism by which it exerts these effects is complex.
One target for activity of chemopreventive drugs against cancers such as colorectal cancer and solid tumor cancers and adenocarcinomas (such as breast, prostate, lung and heptocellular carcinoma) may be improvement of DNA replication. The fidelity of DNA replication is a product of polymerase accuracy, its proofreading activity, and/or the proficiency of the postreplicational mismatch repair system. Inefficiency of fidelity replication can be a key to the development of human cancer. Chemopreventive drugs that increase such efficiency in colorectal cells could significantly reduce the life-threatening manifestations of cancer and diminish cancer deaths. However, some drugs that may have chemopreventive potential, such as 5-amino salicyclic acid, are inactivated and eliminated from circulation when give systemically; 5-amino-salicyclic acid, when orally administered, does not reach the left colon, where may sporadic and colitis-related colorectal cancers develop.
There remains a need for chemopreventative drugs that, for example, when given orally, remain activated for an amount of time so that such drugs may reach affected areas of the body, or areas of the body at risk for cancer, e.g. the left colon.